For a more in-depth review of atypical depression research, click
here.

Benazzi F.Depression with DSM-IV
atypical features: a marker for bipolar II disorder. Eur
Arch Psychiatry Clin Neurosci 2000;250(1):53-5 "The aim of the study
was to find the prevalence of atypical features in bipolar II depression versus
unipolar depression. Five hundred and fifty seven unipolar and bipolar II depressed
outpatients were interviewed with the Structured Clinical Interview for DSM-IV,
the Montgomery Asberg Depression Rating Scale, and the Global Assessment of Functioning
Scale. DSM-IV atypical features were significantly more common in bipolar II patients
than in unipolar patients (45.4% vs 25.4%, odds ratio 2.4). As the diagnosis of
bipolar II disorder is often based on diagnosis of past hypomania, which may not
be very reliable. depression with atypical features may point to bipolar II disorder
diagnosis." [Abstract]

Cassano
GB, Dell'Osso L, Frank E, Miniati M, Fagiolini A, Shear K, Pini S, Maser J.The bipolar spectrum: a clinical reality in search of diagnostic criteria
and an assessment methodology. J Affect Disord 1999 Aug;54(3):319-28
"Failure to recognize subthreshold expressions of mania contributes to the
frequent under-diagnosis of bipolar disorder. There are several reasons for the
lower rate of recognition of subthreshold manic symptoms, when compared to the
analogous pure depressive ones. These include the lack of subjective suffering,
enhanced productivity, ego-syntonicity, and diurnal and seasonal rhythmicity associated
with many of the manic and hypomanic symptoms, and the psychiatrists' tendency
to subsume persistent or even alternating symptoms among personality disorders.
Furthermore, the central diagnostic importance placed on alterations in mood distracts
clinicians from paying attention to other more subtle but clinically meaningful
symptoms, such as changes in energy, neurovegetative symptoms and distorted cognitions.
Although officially accepted in both ICD-10 and DSM-IV, we believe bipolar II
disorder is underdiagnosed because of inattention to symptoms of hypomania. Moreover,
by requiring the presence of both full-blown hypomanic and major depressive episodes,
current nosology fails to include symptoms or signs which are mild and do not
meet threshold criteria. There is already agreement in the field that such symptoms
are important for depression. We now propose that attention should also be devoted
to mild symptomatic manifestations of a manic diathesis, even if such manifestations
may sometimes enhance quality of life. The term 'spectrum' is used to refer to
the broad range of such manifestations of a disorder from core symptoms to temperamental
traits. Spectrum manifestations may be present during, between, or even in the
absence of, an episode of full-blown disorder. We have developed a structured
clinical interview to assess the mood spectrum (SCI-MOODS) to evaluate the whole
range of depressive and manic symptoms. This instrument is currently undergoing
psychometric testing procedures. Similar to the SCID interview, the SCI-MOODS
interview provides a separate rating for each of the major DSM-IV symptoms, but
the latter also identifies and rates subthreshold and atypical manifestations.
This paper presents the concept of a subthreshold bipolar disorder and discusses
the potential epidemiological, diagnostic and therapeutic relevance of such a
spectrum conditions. We also describe the SCI-MOODS interview used reliably to
identify the occurrence of a bipolar spectrum condition. Obviously a great deal
of systematic research needs to be conducted to ascertain the reliability and
validity of subthreshold bipolarity as summarized in this paper and embodied in
our instrument." [Abstract]

Akiskal
HS.The prevalent clinical spectrum of bipolar disorders: beyond
DSM-IV. J Clin Psychopharmacol 1996 Apr;16(2 Suppl 1):4S-14S
"Based on the author's work and that of collaborators, as well as other contemporaneous
research, this article reaffirms the existence of a broad bipolar spectrum between
the extremes of psychotic manic-depressive illness and strictly defined unipolar
depression. The alternation of mania and melancholia beginning in the juvenile
years is one of the most classic descriptions in clinical medicine that has come
to us from Greco-Roman times. French alienists in the middle of the nineteenth
century and Kraepelin at the turn of that century formalized it into manic-depressive
psychosis. In the pre-DSM-III era during the 1960s and 1970s, North American psychiatrists
rarely diagnosed the psychotic forms of the disease; now, there is greater recognition
that most excited psychoses with a biphasic course, including many with schizo-affective
features, belong to the bipolar spectrum. Current data also support Kraepelin's
delineation of mixed states, which frequently take on psychotic proportions. However,
full syndromal intertwining of depressive and manic states into dysphoric or mixed
mania--as emphasized in DSM-IV--is relatively uncommon; depressive symptoms in
the midst of mania are more representative of mixed states. DSM-IV also does not
formally recognize hypomanic symptomatology that intrudes into major depressive
episodes and gives rise to agitated depressive and/or anxious, dysphoric, restless
depressions with flight of ideas. Many of these mixed depressive states arise
within the setting of an attenuated bipolar spectrum characterized by major depressive
episodes and soft signs of bipolarity. DSM-IV conventions are most explicit for
the bipolar II subtype with major depressive and clear-cut spontaneous hypomanic
episodes; temperamental cyclothymia and hyperthymia receive insufficient recognition
as potential factors that could lead to switching from depression to bipolar I
disorder and, in vulnerable subjects, to predominantly depressive cycling. In
the main, rapid-cycling and mixed states are distinct. Nonetheless, there exist
ultrarapid-cycling forms where morose, labile moods with irritable, mixed features
constitute patients' habitual self and, for that reason, are often mistaken for
"borderline" personality disorder. Clearly, more formal research needs
to be conducted in this temperamental interface between more classic bipolar and
unipolar disorders. The clinical stakes, however, are such that a narrow concept
of bipolar disorder would deprive many patients with lifelong temperamental dysregulation
and depressive episodes of the benefits of mood-regulating agents." [Abstract]

Bottlender
R, Sato T, Kleindienst N, Strauss A, Moller HJ.Mixed depressive
features predict maniform switch during treatment of depression in bipolar I disorder.J
Affect Disord. 2004 Feb;78(2):149-52."BACKGROUND: Case observations imply
that depressed patients with mixed features are of high risk for maniform switch
during acute treatment. METHODS: The medical records of 158 bipolar I depressives
were examined with respect to mixed depressive features at admission, naturalistic
medications, and maniform switch during inpatient treatment. RESULTS: Besides
pharmacological variables, the number of mixed depressive symptoms (flight of
ideas, racing thoughts, logorrhea, aggression, excessive social contact, increased
drive, irritability, and distractibility) at admission was associated with a higher
risk for, and the acceleration of, maniform switch during inpatient treatment.
LIMITATIONS: This was a retrospective study in patients receiving naturalistic
treatment. The cohort was hospital based and thus not representative of the full
range of bipolar affective disorder. CONCLUSIONS: In line with recent studies,
our results underline the factors inherent in subjects at a higher risk of switch.
Investigation of the relationships between several inherent factors and their
interactions with pharmacological treatments may be important in resolving the
controversy surrounding antidepressant-induced mania. Further validation studies
on mixed depression are warranted." [Abstract]

Akiskal
HS, Benazzi F.Family history validation of the bipolar nature of
depressive mixed states.J Affect Disord. 2003 Jan;73(1-2):113-22."BACKGROUND:
Recent data indicate that depressive mixed states (DMX), major depressive episode
(MDE) plus few concurrent hypomanic symptoms are common in clinical practice but
omitted in DSM-IV. Our aims were to find the sensitivity and specificity of DMX
for the diagnosis of bipolar II disorder, and validate it against familial bipolarity.
METHODS: 377 consecutive private outpatients presenting with psychoactive drug-free
MDE were interviewed with the Structured Clinical Interview for DSM-IV (Clinician
Version). History of past hypomanic episodes and presence of hypomanic symptoms
during the index MDE were systematically recorded. Of these, 226 were bipolar
II and 151 unipolar. DMX3 was defined as an MDE plus three or more intra-episodic
hypomanic symptoms. RESULTS: DMX3 was present in 58.4% of bipolar II, and 23.1%
of unipolar patients. It was significantly associated with variables distinguishing
bipolar from strictly defined unipolar disorders (younger age at onset, more MDE
recurrence, more atypical features, more bipolar II family history). Unipolar
DMX3 (MDE with documented hypomania solely intra-episodically) was not significantly
different from bipolar II MDE on age at onset, atypical features, and bipolar
II family history. CONCLUSIONS: Results support the inclusion of DMX3 (bipolar
II and 'unipolar') into the bipolar spectrum. Adding the 23% of the UP-DMX3 to
the roster of less-than-manic outpatient depressives will boost the rate of bipolarity
in this outpatient depressive population to a respectable 70%, the highest rate
yet reported for the bipolar spectrum below the threshold of mania." [Abstract]

Benazzi F.Bipolar II depressive mixed
state: finding a useful definition.Compr Psychiatry. 2003
Jan-Feb;44(1):21-7."Recent studies showed that depressive mixed state
(DMX) (major depressive episode [MDE] with few hypomanic symptoms) was common
among depressed outpatients. The aim of the present study was to find a clinicallly
useful definition of DMX. A useful definition could be one increasing the probability
of making the correct diagnosis of bipolar II. Different definitions of DMX were
tested by comparing the sensitivity, specificity, and predictive power for the
diagnosis of bipolar II. Three hundred thirty-six consecutive bipolar II (n =
206) and unipolar (n = 130) MDE outpatients were interviewed with the DSM-IV Structured
Clinical Interview-Clinician Version (SCID-CV). Different DMX definitions were
tested, based on factor analysis, multivariate regression, discriminant analysis,
and logistic regression analysis results. The sensitivity, specificity, correctly
classified, and receiver operating characteristic (ROC) area for bipolar II diagnosis
were compared. Two factors (factor 1, including irritability, psychomotor agitation,
and more talkativeness, and factor 2, including racing thoughts, irritability,
and distractibility) were significantly associated with bipolar II diagnosis.
Of the hypomanic symptoms most common in bipolar II DMX, only irritability and
racing thoughts were significantly associated with bipolar II diagnosis on discriminant
analysis. DMX with three or more concurrent hypomanic symptoms (DMX3) was strongly
associated with bipolar II diagnosis. Comparisons of sensitivity, specificity,
correctly classified, and ROC area of the different DMX definitions (factor 1,
factor 2, DMX3, irritability during MDE, racing thoughts during MDE) for the diagnosis
of bipolar II, showed that factor 1 had the best combination of sensitivity and
specificity, high correctly classified and ROC, but DMX3 has the highest specificity,
and slightly lower correctly classified and ROC than factor 1. A DMX definition
having the highest specificity (DMX3) for bipolar II diagnosis may be more useful
to clinicians, leading to few false positives. Bipolar II diagnosis has important
treatment and clinical implications, but misdiagnosis is common because diagnosis
is often based on history of hypomania (dependent on memory and clinical skills).
A cross-sectional marker like DMX3 may increase the probability of making the
correct diagnosis of bipolar II, and therefore may be a useful definition of DMX."
[Abstract]

Benazzi
F.Depressive mixed state: dimensional versus categorical definitions.Prog
Neuropsychopharmacol Biol Psychiatry. 2003 Feb;27(1):129-34."BACKGROUND:
Recently, there has been a rebirth of studies on depressive mixed state (DMX),
defined as a major depressive episode (MDE) plus few concurrent hypomanic symptoms.
It is still unclear how to best define DMX. The study's aim was to test a categorical
versus a dimensional definition of DMX. METHODS: Consecutive 260 bipolar II disorder
and 173 unipolar MDE outpatients were interviewed with the Structured Clinical
Interview for DSM-IV, when presenting for MDE treatment (drug-free). Hypomanic
symptoms during index MDE were systematically assessed and graded by a hypomania
rating scale (Hypomania Interview Guide, HIG). Different cutoffs of the HIG to
define DMX were tested versus a categorical definition of DMX (requiring more
than two concurrent hypomanic symptoms, DMX3). Sensitivity and specificity for
predicting bipolar II diagnosis were compared. The best definition of DMX based
on the HIG was also compared to DMX3 versus typical bipolar variables (early onset,
many recurrences, atypical features, bipolar family history). RESULTS: An HIG
cutoff of 8 had a specificity for predicting bipolar II diagnosis similar to that
of DMX3. HIG>8 was strongly associated with bipolar family history (an important
external diagnostic validator), and DMX3 was significantly associated with more
bipolar variables (including bipolar family history). LIMITATION: The interview
was done by a single interviewer. CONCLUSIONS: Similar specificity for predicting
bipolar II disorder diagnosis and a similar strong association with bipolar family
history suggest that a categorical and a dimensional definition of DMX could have
similar validity. However, the dimensional definition (based on the scoring of
a hypomania rating scale) could lead to a better assessment of hypomanic symptoms,
resulting in more correct diagnoses of DMX." [Abstract]

Benazzi
F.Which could be a clinically useful definition of depressive mixed
state?Prog Neuropsychopharmacol Biol Psychiatry. 2002 Oct;26(6):1105-11."Depressive
mixed state (DMX) (major depressive episode [MDE] with few superimposed hypomanic
symptoms) was reported to be common among depressed outpatients. Study aim was
to find if the best clinically useful definition of DMX was one based on a minimum
number of hypomanic symptoms, or instead one based on the combination of specific
hypomanic symptoms. METHODS: Consecutive 138 bipolar II and 83 unipolar MDE outpatients
were interviewed with DSM-IV Structured Clinical Interview. DMX definitions tested
were: MDE with three or more hypomanic symptoms (DMX3) and MDE with hypomanic
symptoms irritability, distractibility and racing thoughts. RESULTS: DMX3, and
the combination of racing thoughts, irritability and distractibility, had the
same significant and nonsignificant associations with study variables. DMX3, and
the combination of the specific hypomanic symptoms, significantly predicted bipolar
II diagnosis. For predicting bipolar II diagnosis, DMX3 had higher specificity
(86.7% vs. 50.6%), while the combination of the specific hypomanic symptoms had
higher sensitivity (76.8% vs. 51.4%). CONCLUSIONS: A DMX definition with higher
specificity (DMX3) for predicting bipolar II diagnosis may be more clinically
useful because it may reduce misdiagnosis." [Abstract]

Benazzi
F, Akiskal HS.Delineating bipolar II mixed states in the Ravenna-San
Diego collaborative study: the relative prevalence and diagnostic significance
of hypomanic features during major depressive episodes.
J Affect Disord 2001 Dec;67(1-3):115-22 "BACKGROUND: Depressive mixed
state (DMX), defined by hypomanic features during a major depressive episode (MDE)
is under-researched. Accordingly, study aims were to find DMX prevalence in unipolar
major depressive disorder (MDD) and bipolar II depressive phase, to delineate
the most common hypomanic signs and symptoms during DMX, and to assess their sensitivity
and specificity for the diagnosis of DMX and bipolar II. METHODS: 161 unipolar
and bipolar II MDE psychotropic drug- and substance-free consecutive outpatients
were interviewed during an MDE with the Structured Clinical Interview for DSM-IV.
DMX was defined at two threshold levels as an MDE with two or more (DMX2), and
with three or more (DMX3) simultaneous intra-episode hypomanic signs and symptoms.
RESULTS: DMX2 was present in 73.1% of bipolar II, and in 42.1% of unipolar MDD
(P<0.000); DMX3 was present in 46.3% of bipolar II, and in 7.8% of unipolar
MDD (P<0.000). The most common hypomanic manifestations during MDE were irritability,
distractibility, and racing thoughts. Irritability had the best combination of
sensitivity and specificity for the diagnosis of DMX2 and DMX3. Various combinations
of irritability, distractibility, and racing thoughts correctly classified the
highest number of DMX2 and DMX3, and had the strongest predictive power. DMX2
had high sensitivity and low specificity for bipolar II, whereas DMX3 had low
sensitivity (46.3%) and high specificity (92.1%). LIMITATIONS: Single interviewer,
cross-sectional assessment, and interviewing clinician not blind to patients'
unipolar vs. bipolar status. CONCLUSIONS: When conservatively defined (>or
= 3 intra-episode hypomanic signs and symptoms during MDE), DMX is prevalent in
the natural history of bipolar II but uncommon in unipolar MDD. These findings
have treatment implications, because of growing concerns that antidepressants
may worsen DMX, which in turn may respond better to mood stabilizers. These data
also have methodological implications for diagnostic practice: rather than solely
depending on the vagaries of the patient's memory for past hypomanic episodes,
the search for hypomanic features--ostensibly elation would not be one of those--during
an index depressive episode could enhance the detection of bipolar II in otherwise
pseudo-unipolar patients. Strict adherence to current clinical diagnostic interview
instruments (e.g. the SCID) would make such detection difficult, if not impossible."
[Abstract]

Cassidy
F, Ahearn E, Murry E, Forest K, Carroll BJ.Diagnostic depressive
symptoms of the mixed bipolar episode. Psychol Med 2000
Mar;30(2):403-11 "BACKGROUND: There is not yet consensus on the best
diagnostic definition of mixed bipolar episodes. Many have suggested the DSM-III-R/-IV
definition is too rigid. We propose alternative criteria using data from a large
patient cohort. METHODS: We evaluated 237 manic in-patients using DSM-III-R criteria
and the Scale for Manic States (SMS). A bimodally distributed factor of dysphoric
mood has been reported from the SMS data. We used both the factor and the DSM-III-R
classifications to identify candidate depressive symptoms and then developed three
candidate depressive symptom sets. Using ROC analysis we determined the optimal
threshold number of symptoms in each set and compared the three ROC solutions.
The optimal solution was tested against the DSM-III-R classification for crossvalidation.
RESULTS: The optimal ROC solution was a set, derived from both the DSM-III-R and
the SMS, and the optimal threshold for diagnosis was two or more symptoms. Applying
this set iteratively to the DSM-III-R classification produced the identical ROC
solution. The prevalence of mixed episodes in the cohort was 13.9% by DSM-III-R,
20.2% by the dysphoria factor and 27.4% by the new ROC solution. CONCLUSIONS:
A diagnostic set of six dysphoric symptoms (depressed mood, anhedonia, guilt,
suicide, fatigue and anxiety), with a threshold of two symptoms, is proposed for
a mixed episode. This new definition has a foundation in clinical data, in the
proved diagnostic performance of the qualifying symptoms, and in ROC validation
against two previous definitions that each have face validity." [Abstract]

Cassidy
F, Carroll BJ.The clinical epidemiology of pure and mixed manic
episodes. Bipolar Disord 2001 Feb;3(1):35-40 "INTRODUCTION:
Few large clinical epidemiological studies have been undertaken comparing subjects
meeting criteria for mixed and pure states of bipolar disorder. In part, the difficulty
comparing these states emanates from confusion in their diagnostic separation.
In the current report, we use a definition derived from receiver operating characteristic
(ROC) curve analysis as an alternative to the DSM-IIIR/IV definition, and we compare
the two subtypes of manic episodes. METHODS: Three hundred and sixty-six patients
meeting DSM-IIIR criteria for bipolar disorder, manic or mixed, were categorized
using newly described criteria for mixed states. The two subtypes were compared
on demographic variables and clinical history variables, using multiple analysis
of variance with post hoc univariate F tests. The same analyses were conducted
using the DSM-IIIR-defined subtypes. RESULTS: Using the ROC criteria, 79 subjects
(21.6%) were characterized as mixed, in contrast to 51 subjects (13.9%) using
DSM-IIIR criteria for bipolar disorder, mixed. The ROC-defined mixed manic group
comprised more Caucasians and more females. Age of first psychiatric hospitalization
was earlier and duration of illness longer in the mixed group. First episodes
were unlikely to be categorized as mixed (< 5%). When the DSM-IIIR definition
was employed, differences were not demonstrated. CONCLUSIONS: An earlier age of
first psychiatric hospitalization and increased duration of illness, as well as
a lower frequency of mixed subtype of manic episode during first hospitalization,
are compatible with the view that mixed manic episodes occur more frequently later
in the course of bipolar disorder. Moreover, differences in race, sex, and clinical
histories of subjects in mixed episodes tend to support the separation of mixed
mania as a diagnostic subtype of bipolar disorder." [Abstract]

Cassidy
F, Murry E, Forest K, Carroll BJ.Signs and symptoms of mania in
pure and mixed episodes. J Affect Disord 1998 Sep;50(2-3):187-201
"BACKGROUND: Debate continues about the diagnosis of mixed mania and the
restrictiveness of the DSM-III-R and DSM-IV criteria for Bipolar Disorder, mixed.
Although awareness of dysphoric features during mania continues to grow, standard
mania rating instruments do not adequately assess mixed states and there is a
striking disparity between the dysphoric signs and symptoms emphasized in research
studies and the commonly employed DSM criteria. METHODS: Three hundred sixteen
inpatients meeting DSM-III-R criteria for Bipolar Disorder, manic or mixed, were
evaluated by rating 20 signs and symptoms. The frequencies of these signs and
symptoms were computed for both diagnostic subtypes and compared using chi2 statistics
and conditional probability parameters. RESULTS: The most frequently noted signs
and symptoms in mania are motor activation, accelerated thought process, pressured
speech and decreased sleep. Although euphoric mood was present in a large portion
of the cohort, irritability, dysphoric mood and mood lability were also prominent
in the entire cohort. Dysphoric mood, mood lability, anxiety, guilt, suicidality,
and irritability were the only symptoms significantly more common in the mixed
group. In contrast, grandiosity, euphoric mood, and pressured speech were significantly
more often observed in the pure manic group. Contrary to popular belief, paranoia
did not differ significantly between the two groups. Suicidality was present in
a non-trivial 7% of the entire cohort, including some subjects who did not meet
the criteria for mixed mania. LIMITATIONS: The comparison of mixed and manic episodes
requires the appropriate definition of mixed states. In the current report we
use the DSM-III-R definition of Bipolar Disorder, mixed, which may be too rigid.
CONCLUSIONS: The data underscore that mania is not a purely euphoric state. Substantial
rates of dysphoria, lability, anxiety and irritability were noted in the "pure"
manic patients, as well as in those who meet the full DSM criteria for Bipolar
Disorder, mixed, suggesting, that perhaps a less restrictive definition of mixed
states would be more appropriate." [Abstract]

Brieger
P, Roettig S, Ehrt U, Wenzel A, Bloink R, Marneros A.TEMPS-a scale
in 'mixed' and 'pure' manic episodes: new data and methodological considerations
on the relevance of joint anxious-depressive temperament traits.J
Affect Disord. 2003 Jan;73(1-2):99-104."BACKGROUND: Temperament is an
important factor in affective illness. There is some indication that mixed episodes
result from an admixture of inverse temperamental factors (e.g. depressive and/or
anxious) to a manic syndrome. To test this hypothesis, which has been first formulated
by Akiskal [Clin. Neuropharmacol. 15 (Suppl. 1A) (1992) 632-633], we compared
the temperament of non-acute bipolar affective patients with and without the history
of a previous mixed episode. METHODS: Patients who had been hospitalized for a
bipolar disorder were re-assessed at least 6 months after their last in-patient
treatment. Those who met the criteria for a partially remitted or full affective
or psychotic episode at re-assessment were excluded from the study. Data concerning
illness history, current psychopathology (SCID-I interview), depression (BDI),
mania (Self-Report Manic Inventory) and temperament (TEMPS-A scale) were obtained.
Patients with and without a history of previous mixed episodes were compared.
RESULTS: Of 49 eligible former patients, 22 subjects with and 23 subjects without
a former mixed episode in bipolar affective disorder fulfilled the inclusion criteria.
Subjects suffering from bipolar affective disorder exhibited significantly more
depressive and anxious and less hyperthymic temperament, if they had experienced
a mixed episode previously. Concerning cyclothymic and irritable temperament,
bipolar affective patients with a former mixed episode presented non-significantly
higher scores. Patients with a former mixed episode presented with higher depression
scores than patients without such a history. No group differences were found concerning
current mania scores. LIMITATIONS: (1). This is a preliminary report from an ongoing
study. (2). Temperament had not been assessed premorbidly. (3). Although group
comparisons revealed significant differences, these did not seem great enough
to fully explain the emergence of a mixed episode. CONCLUSION: Our findings support
the study's hypothesis that mixed episodes occur more often in subjects with an
inverse temperament (e.g. depressive and anxious), although it cannot be ruled
out that subsyndromal features of the bipolar illness had an effect on temperament
assessment." [Abstract]

Goldberg JF, Garno JL, Portera L, Leon AC, Kocsis
JH.Qualitative differences in manic symptoms during mixed versus
pure mania. Compr Psychiatry 2000 Jul-Aug;41(4):237-41
"Previous studies have compared demographic and clinical-outcome features
of bipolar patients with mixed or pure mania. However, little is known about the
potential differences in the nature and extent of manic symptoms in mania either
with or without an accompanying depression. This study examined DSM-III-R manic
symptoms in a cohort of 183 bipolar I inpatients hospitalized for mixed mania
(diagnosed by broad or narrow criteria) or pure manic episodes. Inpatient charts
were reviewed to determine the presence of individual affective symptoms. The
results indicate that clinicians were more likely to diagnose a pure mania from
the beginning to end of an episode than to diagnose a mixed mania from its beginning
to end. Mixed-manic patients had significantly fewer manic symptoms than pure
manic patients. Grandiosity, euphoria, pressured speech, and a decreased need
for sleep were more prevalent during pure versus mixed mania. Grandiosity and
a diminished need for sleep were especially notable during pure mania compared
with mixed mania as defined by narrow criteria for mixed states. The observed
differences in manic symptom profiles between mixed and pure mania may aid in
the clinical assessment of dysphoric states among bipolar patients. The data also
lend support to the use of broad diagnostic criteria for defining mixed mania
as an entity phenomenologically distinct from pure mania." [Abstract]

Brieger
P, Ehrt U, Roettig S, Marneros A.Personality features of patients
with mixed and pure manic episodes.Acta Psychiatr Scand.
2002 Sep;106(3):179-82."OBJECTIVE: To test the hypothesis that patients
with a mixed manic episode show different personality features than patients with
a pure manic episode. METHOD: Sixteen patients with a mixed manic episode (broad
criteria) and 26 patients with a pure manic episode were assessed with diagnostic
interviews (SCID I/II) as well as instruments for depression, mania and personality.
RESULTS: Even after controlling for age as well as depression and mania score
at assessment, no differences between the two groups emerged concerning either
personality features as assessed with the NEO-five-factor inventory (NEO-FFI)
or personality disorders. CONCLUSION: We found no difference between patients
with mixed mania and patients with pure mania concerning their personality features.
Possible reasons for this are being discussed." [Abstract]

Perugi
G, Micheli C, Akiskal HS, Madaro D, Socci C, Quilici C, Musetti L.Polarity
of the first episode, clinical characteristics, and course of manic depressive
illness: a systematic retrospective investigation of 320 bipolar I patients.Compr
Psychiatry 2000 Jan-Feb;41(1):13-8"In 320 patients with established bipolar
I disorder, we examined the past course on the basis of polarity at onset (depressive,
mixed, and manic). Despite the obvious limitations of retrospective methodology,
information on course parameters in a large sample of affective disorders is most
practically obtained by such methodology. We believe that our systematic interview
of patients and their relatives--as well as the systematic study of their records--minimized
potential biases. Depressive onsets were the most common, accounting for 50%,
followed by mixed and manic onsets in about equal proportion. In general, the
polarity of episodes over time reflected polarity at onset. Those with depressive
onset had significantly higher levels of rapid cycling, as well as suicide attempts,
but were significantly less likely to develop psychotic symptoms. Mixed onsets,
too, had high rates of suicide attempts, but differed from depressive onsets in
having significantly more chronicity yet negligible rates of rapid cycling at
follow-up evaluation. Because cases with depressive onset had received significantly
higher rates of psychopharmacologic treatment, our data are compatible with the
hypothesis that antidepressants may play a role in the induction of rapid cycling.
Overall, our data support the existence of distinct longitudinal patterns within
bipolar I disorder, which in turn appear correlated with the polarity at onset.
In particular, rapid cycling and mixed states emerge as distinct psychopathologic
processes." [Abstract]

Benazzi
F.Psychomotor changes in melancholic and atypical depression: unipolar
and bipolar-II subtypes. Psychiatry Res 2002 Nov 15;112(3):211-20
"Psychomotor changes are reported to be 'nearly always present' in the melancholic
subtype of major depressive episode (MDE) in DSM-IV-TR, and are believed by some
researchers to be markers of melancholia. The aim of this study was to compare
melancholic and atypical forms of MDE and to determine whether psychomotor changes
are core features of melancholic MDE. The Structured Clinical Interview of DSM-IV
was used to consecutively assess 107 unipolar and 164 bipolar-II MDE outpatients.
The criteria used to define melancholic and atypical MDE followed DSM-IV-TR. Melancholic
MDE was present in 17.7% of patients; atypical MDE, in 35.0%. The group of patients
with melancholic MDE had the following differences from the atypical group: higher
age, higher age at onset, fewer females, more unipolar cases, fewer bipolar-II
cases, lower Global Assessment of Functioning scores, more MDE symptoms, and more
psychotic features. Percentages of observable and marked psychomotor changes (agitation
and retardation combined) did not differ significantly between the two groups,
though the melancholic group tended to have more symptoms. Retardation was significantly
more common in melancholic MDE, but its frequency was very low in both melancholic
and atypical cases (12.5 vs. 0.0%). Logistic regression controlling for age, gender
and illness duration had little effect on the findings, which suggests that psychomotor
changes are not core features of melancholic MDE." [Abstract]

Keck
PE Jr, McElroy SL, Havens JR, Altshuler LL, Nolen WA, Frye MA, Suppes T, Denicoff
KD, Kupka R, Leverich GS, Rush AJ, Post RM.Psychosis in bipolar
disorder: phenomenology and impact on morbidity and course of illness.Compr
Psychiatry. 2003 Jul-Aug;44(4):263-9."Although psychosis is common in
bipolar disorder, few studies have examined the prognostic significance of psychotic
features. In addition, some studies suggest that the presence of mood-incongruent
psychosis, in particular, is associated with poorer outcome compared with mood-congruent
psychosis. We assesses the phenomenology and prevalence of mood-congruent and
mood-incongruent psychotic symptoms in 352 patients with bipolar I disorder participating
in the Stanley Foundation Bipolar Treatment Network. We compared the demographic
and clinical features, and measures of psychosocial and vocational functioning
in patients with and without a history of psychosis. The phenomenology of psychosis
in this cohort of patients with bipolar disorder was similar to that reported
in earlier studies and supported the lack of diagnostic specificity of any one
type of psychotic symptom. There were no significant differences between patients
with and without a history of psychosis on any demographic, psychosocial, vocational,
or course of illness variables. Only family history of bipolar disorder was significantly
more common in patients with nonpsychotic bipolar disorder compared to patients
with a history of psychosis. Among bipolar patients with a history of psychosis,
only the proportion of women and lifetime prevalence rates of anxiety disorders
occurred significantly more in patients with mood-incongruent delusions. In this
large cohort of outpatients with bipolar I disorder, neither a history of psychosis
nor of mood-incongruent psychosis had prognostic significance at entry into the
Network. The lack of observable prognostic impact may have been, in part, due
to the relatively high morbidity and poor functional outcome of a substantial
portion of the total cohort." [Abstract]

Yildiz
A, Sachs GS.Age onset of psychotic versus non-psychotic bipolar
illness in men and in women. J Affect Disord. 2003 Apr;74(2):197-201."OBJECTIVE:
To investigate the relationship between psychotic symptoms and age at onset of
bipolar illness. METHOD: The charts of bipolar patients treated at the Massachusetts
General Hospital Bipolar Clinic were reviewed for age of first affective episode,
demographics and history of psychotic symptoms. RESULTS: Data was obtained for
328 bipolar patients (56.7% females) of whom 42% had psychotic symptoms sometime
through the course of their illness. Overall, there was no significant difference
in age of onset between the psychotic and non-psychotic groups. Additional analysis
carried out separately by gender found significant difference for males but not
for females. Age at onset for psychotic males was significantly lower than non-psychotic
males. Psychosis was less common in males than females. The mean age of onset
for psychotic males was significantly lower than psychotic females. CONCLUSION:
This result implies that developmental physiology underlying psychosis in bipolar
illness may differ for men and women. The different proportions of males and females
in the study samples may account for conflicting results reported in the literature
for age of onset of psychotic bipolar illness." [Abstract]

Gonzalez-Pinto A, van Os J, Perez de Heredia JL,
Mosquera F, Aldama A, Lalaguna B, Gutierrez M, Mico JA.Age-dependence
of Schneiderian psychotic symptoms in bipolar patients.Schizophr
Res. 2003 Jun 1;61(2-3):157-62."Psychotic symptoms frequently occur in
bipolar disorder, especially in younger patients. However, whether the association
with younger age also extends to psychotic symptoms that have traditionally been
associated with schizophrenia, such as Schneiderian first-rank symptoms (FRSs),
is unclear. This study examined FRSs in bipolar I patients and their relationship
to age and gender. The sample comprised 103 consecutive inpatients who met DSM
IV criteria for bipolar disorder, manic or mixed. FRSs were rated with the Scale
for the Assessment of Positive Symptoms (SAPS). Interaction between FRSs and gender
and FRSs and age was assessed using logistic regression. A high rate of FRSs in
manic and mixed patients was found with a higher frequency in men (31%) than in
women (14%; P=0.038). A monotonic increase in the association between FRSs and
younger age was apparent (odds ratios (OR) over five levels: 1.42; 1.00-2.01).
These results confirm previous findings that FRSs are not specific to schizophrenia
and suggest in addition that a dimension of nuclear psychotic experiences of developmental
origin extends across categorically defined psychotic disorders." [Abstract]

Dell'Osso
L, Pini S, Tundo A, Sarno N, Musetti L, Cassano GB.Clinical characteristics
of mania, mixed mania, and bipolar depression with psychotic features.
Compr Psychiatry 2000 Jul-Aug;41(4):242-7 "This study investigated a
series of clinical characteristics, including the level of insight into illness
and axis I comorbidity, in 125 patients with bipolar disorder with psychotic features
categorized in three groups: 62 patients with mania, 28 patients with mixed mania,
and 35 patients with depression. All patients were hospitalized and were assessed
in the week preceding discharge. The three groups did not differ in the severity
of psychopathology as assessed by the Brief Psychiatric Rating Scale (BPRS). The
mania group had a lower level of insight into the social consequences of illness
than the other two groups, and compared with the group with depression, they had
a lower level of insight of poor attention and of poor social judgment. As to
axis I comorbidity, obsessive-compulsive disorder was found to be significantly
more frequent in depression than in mania. Patients with depression more frequently
reported a history of suicidality than those with mania, whereas they did not
significantly differ from patients with mixed mania. Our results suggest that
mixed mania as assessed at the time of the patient's discharge differs from mania
and from depression with respect to a limited number of features among those examined.
However, the overall level of insight into illness significantly discriminated
mixed mania from mania, but not from depression." [Abstract]

DelBello
MP, Carlson GA, Tohen M, Bromet EJ, Schwiers M, Strakowski SM.Rates
and predictors of developing a manic or hypomanic episode 1 to 2 years following
a first hospitalization for major depression with psychotic features.J
Child Adolesc Psychopharmacol. 2003 Summer;13(2):173-85."INTRODUCTION:
Although the presence of psychosis during major depression has been identified
as a predictor of later developing mania or hypomania, to our knowledge there
have been no studies examining rates and predictors of developing a manic or hypomanic
episode in patients who were admitted for their first psychiatric hospitalization
for major depressive disorder with psychosis (MDDP). METHODS: Patients admitted
for their first psychiatric hospitalization, with a Diagnostic and Statistical
Manual of Mental Disorders (fourth edition) diagnosis of MDDP, were recruited
from three sites (N = 157) and evaluated prospectively for up to 2 years to identify
new symptoms of mania or hypomania. Family history was assessed using the Family
History-Research Diagnostic Criteria Interview. Clinical and demographic factors
associated with developing a manic or hypomanic episode were identified using
stepwise logistic regression. RESULTS: Thirteen percent (n = 21) of patients with
MDDP developed mania or hypomania within the follow-up period. Family history
of affective disorders and age at onset of MDDP were not predictive of switch.
MDDP patients who were treated with antidepressants were four times less likely
to develop mania or hypomania than those who were not treated with antidepressants,
after controlling for site differences. CONCLUSIONS: Our findings suggest that
within the first 1 to 2 years following first hospitalization for MDDP, a subset
of patients will develop mania or hypomania. Additionally, our data suggest that
antidepressant exposure does not increase the risk of, and may be protective against,
developing a manic or hypomanic episode in patients hospitalized for MDDP."
[Abstract]

Akiskal
HS, Hantouche EG, Bourgeois ML, Azorin JM, Sechter D, Allilaire JF, Lancrenon
S, Fraud JP, Chatenet-Duchene L.Gender, temperament, and the clinical
picture in dysphoric mixed mania: findings from a French national study (EPIMAN).
J Affect Disord 1998 Sep;50(2-3):175-86 "BACKGROUND: This research derives
from the French national multisite collaborative study on the clinical epidemiology
of mania (EPIMAN). Our aim is to establish the validity of dysphoric mania along
a "spectrum of mixity" extending into mixed mania with subthreshold
depressive manifestations; to demonstrate the feasibility of obtaining clinically
meaningful data on this entity on a national level; and to characterize the contribution
of temperamental attributes and gender in its origin. METHODS: EPIMAN involves
training 23 French psychiatrists in four different sites, representing four regions
of France; to rigorously apply a common protocol deriving from the criteria of
DSM-IV and McElroy et al.; the use of such instruments as the Beigel-Murphy, Ahearn-Carroll,
modified HAM-D; and measures of affective temperaments based on the Akiskal-Mallya
criteria; obtaining data on comorbidity, and family history (according to Winokur's
approach as incorporated into the FH-RDC); and prospective follow-up for at least
12 months. The present report concerns the clinical and temperamental features
of 104 manic patients during the acute hospital phase. RESULTS: Dysphoric mania
(DM defined conservatively with fullblown depressive admixtures of five or more
symptoms) occurred in 6.7%; the rate of dysphoric mania defined broadly (DM, presence
of > or = 2 depressive symptoms) was 37%. Depressed mood and suicidal thoughts
had the best positive predictive values for mixed mania. In comparison to pure
mania (0-1 depressive symptoms), DM was characterized by female over-representation;
lower frequency of such typical manic symptomatology as elation, grandiosity,
and excessive involvement; higher prevalence of associated psychotic features;
higher rate of mixed states in first episodes; and complex temperamental dysregulation
along primarily depressive, but also cyclothymic, and irritable dimensions; such
irritability was particularly apparent in mixed mania at the lowest threshold
of depressive admixtures of two symptoms only. LIMITATION: In a study involving
hospitalized affectively unstable psychotic patients, it was difficult to assure
that psychiatrists making the clinical diagnoses would be blind to the temperamental
measures. However, bias was minimized by the systematic and/or semi-structured
nature of all evaluations. CONCLUSIONS: Mixed mania, defined cross-sectionally
by the simultaneous presence of at least two depressive symptoms, represents a
prevalent and clinically distinct form of mania. Subthreshold depressive admixtures
with mania actually appear to represent the more common expression of dysphoric
mania. Moreover, an irritable dimension appears to be relevant to the definition
of the expression of mixed mania with the lowest threshold of depressive symptoms.
Neither an extreme, nor an endstage of mania, "mixity" is best conceptualized
as intrusion of mania into its "opposite" temperament - especially that
defined by lifelong depressive traits - and favored by female gender. These data
suggest that reversal from a temperament to an episode of "opposite"
polarity represents a fundamental aspect of the dysregulation that characterizes
bipolar disorder. In both men and women with hyperthymic temperament, there appears
"protection" against depressive symptom formation during a manic episode
which, accordingly, remains relatively "pure". Because men have higher
rates of this temperament, pure mania is overrepresented in men; on the other
hand, the depressive temperament in manic women seems to be a clinical marker
for the well-known female tendency for depression, hence the higher prevalence
of mixed mania in women." [Abstract]

Benazzi
F.Should mood reactivity be included in the DSM-IV atypical features
specifier? Eur Arch Psychiatry Clin Neurosci 2002 Jun;252(3):135-40
"BACKGROUND: The definition of atypical depression is still an unsolved issue.
DSM-IV atypical features specifier criteria always require mood reactivity, but
why mood reactivity should be included is unclear. The study aim was to test whether
mood reactivity should be included in DSM-IV atypical features specifier. METHODS:
Consecutively, 164 unipolar and 241 "soft" bipolar II major depressive
episode (MDE) outpatients were interviewed with the Structured Clinical Interview
for DSM-IV. The DSM-IV criteria for atypical features specifier were strictly
followed. Associations were tested by univariate logistic regression. RESULTS:
MDE with atypical features was present in 41.4 % of patients. Bipolar II disorder
was significantly more common in patients with atypical features. MDE with atypical
features was significantly associated with bipolar II, female gender, lower age
of onset, more axis I comorbidity, fewer psychotic features, and more depressive
mixed states. In the whole sample, mood reactivity was significantly associated
with all the atypical symptoms, apart from leaden paralysis, and all the other
atypical symptoms were significantly associated with each other. In the bipolar
II sub-sample, mood reactivity was associated with many, but not all, atypical
symptoms, while in the unipolar sub-sample it was associated with no atypical
symptom. Atypical symptoms were significantly more common in mood reactive than
in non-mood reactive patients, apart from leaden paralysis. Bipolar II disorder
and mood reactivity were strongly associated. CONCLUSIONS: Results may support
the inclusion of mood reactivity in the DSM-IV atypical features specifier for
bipolar II disorder, but not for unipolar depression." [Abstract]

Pini S, Dell'Osso L, Mastrocinque C, Marcacci G, Papasogli
A, Vignoli S, Pallanti S, Cassano G.Axis I comorbidity in bipolar
disorder with psychotic features. Br J Psychiatry 1999
Nov;175:467-71 "BACKGROUND: Axis I comorbidities are prevalent among
patients with severe bipolar disorder but the clinical and psychopathological
implications are not clear. AIMS: To investigate characteristics of four groups
of patients categorised as follows: substance abuse only (group 1), substance
abuse associated with other Axis I disorders (group 2), non-substance-abuse Axis
I comorbidity (group 3), no psychiatric comorbidity (group 4). METHOD: Consecutive
patients with bipolar disorder with psychotic features (n = 125) were assessed
using the Structured Clinical Interview for DSM-III-R--patient version, and several
psychopathological scales. RESULTS: By comparison with group 4, group 1 had a
higher risk of having mood-incongruent delusions, group 2 had an earlier age at
onset of mood disorder, a more frequent onset with a mixed state and a higher
risk of suicide, and group 3 had more severe anxiety and a better awareness of
illness. CONCLUSIONS: Substance abuse, non-substance-abuse Axis I comorbidity
and their reciprocal association are associated with different characteristics
of bipolar disorder." [Abstract]

Akiskal HS, Bourgeois ML, Angst J, Post R, Moller
H, Hirschfeld R.Re-evaluating the prevalence of and diagnostic
composition within the broad clinical spectrum of bipolar disorders.
J Affect Disord 2000 Sep;59 Suppl 1:S5-S30 "Until recently it was believed
that no more than 1% of the general population has bipolar disorder. Emerging
transatlantic data are beginning to provide converging evidence for a higher prevalence
of up to at least 5%. Manic states, even those with mood-incongruent features,
as well as mixed (dysphoric) mania, are now formally included in both ICD-10 and
DSM-IV. Mixed states occur in an average of 40% of bipolar patients over a lifetime;
current evidence supports a broader definition of mixed states consisting of full-blown
mania with two or more concomitant depressive symptoms. The largest increase in
prevalence rates, however, is accounted for by 'softer' clinical expressions of
bipolarity situated between the extremes of full-blown bipolar disorder where
the person has at least one manic episode (bipolar I) and strictly defined unipolar
major depressive disorder without personal or family history for excited periods.
Bipolar II is the prototype for these intermediary conditions with major depressions
and history of spontaneous hypomanic episodes; current evidence indicates that
most hypomanias pursue a recurrent course and that their usual duration is 1-3
days, falling below the arbitrary 4-day cutoff required in DSM-IV. Depressions
with antidepressant-associated hypomania (sometimes referred to as bipolar III)
also appear, on the basis of extensive international research neglected by both
ICD-10 and DSM-IV, to belong to the clinical spectrum of bipolar disorders. Broadly
defined, the bipolar spectrum in studies conducted during the last decade accounts
for 30-55% of all major depressions. Rapid-cycling, defined as alternation of
depressive and excited (at least four per year), more often arise from a bipolar
II than a bipolar I baseline; such cycling does not in the main appear to be a
distinct clinical subtype - but rather a transient complication in 20% in the
long-term course of bipolar disorder. Major depressions superimposed on cyclothymic
oscillations represent a more severe variant of bipolar II, often mistaken for
borderline or other personality disorders in the dramatic cluster. Moreover, atypical
depressive features with reversed vegetative signs, anxiety states, as well as
alcohol and substance abuse comorbidity, is common in these and other bipolar
patients. The proper recognition of the entire clinical spectrum of bipolarity
behind such 'masks' has important implications for psychiatric research and practice.
Conditions which require further investigation include: (1) major depressive episodes
where hyperthymic traits - lifelong hypomanic features without discrete hypomanic
episodes - dominate the intermorbid or premorbid phases; and (2) depressive mixed
states consisting of few hypomanic symptoms (i.e., racing thoughts, sexual arousal)
during full-blown major depressive episodes - included in Kraepelin's schema of
mixed states, but excluded by DSM-IV. These do not exhaust all potential diagnostic
entities for possible inclusion in the clinical spectrum of bipolar disorders:
the present review did not consider cyclic, seasonal, irritable-dysphoric or otherwise
impulse-ridden, intermittently explosive or agitated psychiatric conditions for
which the bipolar connection is less established. The concept of bipolar spectrum
as used herein denotes overlapping clinical expressions, without necessarily implying
underlying genetic homogeneity. In the course of the illness of the same patient,
one often observes the varied manifestations described above - whether they be
formal diagnostic categories or those which have remained outside the official
nosology. Some form of life charting of illness with colored graphic representation
of episodes, stressors, and treatments received can be used to document the uniquely
varied course characteristic of each patient, thereby greatly enhancing clinical
evaluation." [Abstract]

Perugi
G, Toni C, Travierso MC, Akiskal HS.The role of cyclothymia in
atypical depression: toward a data-based reconceptualization of the borderline-bipolar
II connection. J Affect Disord 2003 Jan;73(1-2):87-98
"OBJECTIVE: Recent data, including our own, indicate significant overlap
between atypical depression and bipolar II. Furthermore, the affective fluctuations
of patients with these disorders are difficult to separate, on clinical grounds,
from cyclothymic temperamental and borderline personality disorders. The present
analyses are part of an ongoing Pisa-San Diego investigation to examine whether
interpersonal sensitivity, mood reactivity and cyclothymic mood swings constitute
a common diathesis underlying the atypical depression-bipolar II-borderline personality
constructs. METHOD: We examined in a semi-structured format 107 consecutive patients
who met criteria for major depressive episode with DSM-IV atypical features. Patients
were further evaluated on the basis of the Atypical Depression Diagnostic Scale
(ADDS), the Hopkins Symptoms Check-list (HSCL-90), and the Hamilton Rating Scale
for Depression (HRSD), coupled with its modified form for reverse vegetative features
as well as Axis I and SCID-II evaluated Axis II comorbidity, and cyclothymic dispositions
('APA Review', American Psychiatric Press, Washington DC, 1992). RESULTS: Seventy-eight
percent of atypical depressives met criteria for bipolar spectrum-principally
bipolar II-disorder. Forty-five patients who met the criteria for cyclothymic
temperament, compared with the 62 who did not, were indistinguishable on demographic,
familial and clinical features, but were significantly higher in lifetime comorbidity
for panic disorder with agoraphobia, alcohol abuse, bulimia nervosa, as well as
borderline and dependent personality disorders. Cyclothymic atypical depressives
also scored higher on the ADDS items of maximum reactivity of mood, interpersonal
sensitivity, functional impairment, avoidance of relationships, other rejection
avoidance, and on the interpersonal sensitivity, phobic anxiety, paranoid ideation
and psychoticism of the HSCL-90 factors. The total number of cyclothymic traits
was significantly correlated with 'maximum' reactivity of mood and interpersonal
sensitivity. A significant correlation was also found between interpersonal sensitivity
and 'usual' and 'maximum' reactivity of mood. LIMITATION: Correlational study.
CONCLUSIONS: Mood lability and interpersonal sensitivity traits appear to be related
by a cyclothymic temperamental diathesis which, in turn, appears to underlie the
complex pattern of anxiety, mood and impulsive disorders which atypical depressive,
bipolar II and borderline patients display clinically. We submit that conceptualizing
these constructs as being related will make patients in this realm more accessible
to pharmacological and psychological interventions geared to their common temperamental
attributes. More generally, we submit that the construct of borderline personality
disorder is better covered by more conventional diagnostic entities." [Abstract]

Benazzi
F.Depressive mixed state frequency: age/gender effects.Psychiatry
Clin Neurosci. 2002 Oct;56(5):537-43."Depressive mixed state (DMX), a
major depressive episode (MDE) combined with few manic/hypomanic symptoms, is
understudied. Age and gender are important variables in mood disorders. The aim
of the present study was to determine whether age and gender had any effect on
the frequency of DMX. Consecutive unipolar (n = 144) and bipolar II (n = 218)
drug-free MDE out-patients were interviewed with the Structured Clinical Interview
for DSM-IV when presenting for MDE treatment. The presence of hypomanic symptoms
during the index MDE was assessed systematically. Depressive mixed state was defined
as a MDE with three or more concurrent hypomanic symptoms (DMX3), following previous
reports. Associations were tested by logistic regression. The results showed that
the DMX3 frequency was 43.9% and that it affected more females than males. Frequency
decreased with age. The lower frequency with age was related to the lower frequency
of bipolar II disorder with age. Bipolar disorder family history of DMX3 patients
did not change with age. In conclusion, the frequency of DMX3 was high and related
to age. The high frequency of DMX3 supports the clinical usefulness of the definition,
as well as observations that antidepressants may worsen its hypomanic symptoms,
whereas antipsychotics and mood stabilisers may treat them. A bipolar vulnerability
seems to be required for the appearance of DMX3 also in later life." [Abstract]

Benazzi
F.Depressive mixed states: unipolar and bipolar II.
Eur Arch Psychiatry Clin Neurosci 2000;250(5):249-53 "Depressive mixed
states (DMS) (major depressive episodes with some hypomanic symptoms) are understudied,
and not classified in DSM-IV. The study aim was to find prevalence of DMS among
depressed outpatients, to study clinical differences between DMS and non-DMS,
and relationships of DMS with unipolar and bipolar II. Ninety eight consecutive
DSM-IV bipolar II and unipolar depressed outpatients were interviewed with the
Structured Clinical Interview for DSM-IV. DMS was defined as an MDE with at least
two concurrent hypomanic symptoms. DMS was present in 62.2% of patients [48.7%
of unipolar, 71.9% of bipolar II, (p=0.022)]. DMS had significantly fewer unipolar,
more bipolar II patients, lower age at onset, and more atypical features than
non-DMS. Bipolar II DMS had significantly more recurrences, more atypical features,
and lower age at onset (trend) than unipolar DMS. Bipolar II DMS had (trend) lower
age at onset and more atypical features than bipolar II non-DMS. High DMS prevalence
has important treatment implications, as antidepressants may worsen DMS, and some
antidepressant-resistant depressions may be DMS responding to mood stabilizers.
DMS may be distinct from non-DMS, but not from unipolar and bipolar II disorders,
and this distinction may be due mainly to high bipolar II prevalence in DMS."
[Abstract]

Sato
T, Bottlender R, Schroter A, Moller HJ.Frequency of manic symptoms
during a depressive episode and unipolar 'depressive mixed state' as bipolar spectrum.Acta
Psychiatr Scand. 2003 Apr;107(4):268-74."OBJECTIVE: To report the frequency
of intra-episode manic symptoms in depressive episodes, and to evaluate unipolar
depressive mixed state (DMS) as bipolar spectrum. METHOD: A total of 958 (863
unipolar, 25 bipolar II, and 70 bipolar I) depressive in-patients were assessed
in terms of manic symptoms at admission, and several clinical variables using
standardized methods. RESULTS: The frequency of manic symptoms (flight of idea,
logorrhea, aggression, excessive social contact, increased drive, irritability,
racing thoughts, and distractibility) was significantly higher in bipolar depressives
than in unipolar depressives. Unipolar depressives with DMS - defined as having
two or more manic symptoms - had more similarities to bipolar depressives than
to other unipolar depressives in clinical variables such as onset age, family
history of bipolar disorder, and possibly suicidality. CONCLUSION: Depressive
mixed state is frequent, particular in bipolar depressives. Unipolar depressives
with DMS may be better classified into bipolar spectrum." [Abstract]

Sato
T, Bottlender R, Kleindienst N, Tanabe A, Moller HJ.The boundary
between mixed and manic episodes in the ICD-10 classification.Acta
Psychiatr Scand. 2002 Aug;106(2):109-16."OBJECTIVE: To investigate the
boundary between ICD-10 mixed and manic episodes, which has apparently remained
understudied. METHOD: In-patients with ICD-10 mixed (n=36) and manic episodes
(n=145) were compared in terms of demographic, clinical, therapeutical and outcome
variables. RESULTS: Of in-patients with manic episode, 26 (18%) had several depressive
symptoms at admission. These patients (dysphoric manic patients) were very similar
to patients with ICD-10 mixed episode in terms of current symptomatic presentations
and several clinical and therapeutic variables, which were significantly different
from those in patients with pure mania. CONCLUSION: The ICD-10 boundary between
mixed and manic episodes is unlikely to be effective although experienced clinicians
made the diagnoses. The system may have a high probability of diagnosing dysphoric
manic patients as having manic episode, despite their great similarities to patients
with mixed episode in terms of current psychopathological presentations as well
as clinically important variables." [Abstract]

Benazzi
F.The clinical picture of bipolar II outpatient depression in private
practice. Psychopathology 2001 Mar-Apr;34(2):81-4 "Uncertainties
exist about whether depressive episodes differ phenomenologically in unipolar
and bipolar II patients. The aim of the present study was to better define the
clinical picture and course of bipolar II depression. Three hundred and ninety-nine
consecutive outpatients, presenting for treatment of unipolar and bipolar II depression,
were interviewed with the Structured Clinical Interview for DSM-IV, the Montgomery-Asberg
Depression Rating Scale and the Global Assessment of Functioning Scale. Bipolar
II depression had significantly lower age at onset, more recurrences and more
patients with DSM-IV atypical features. Gender, duration of illness, psychosis,
chronicity, severity, axis I comorbidity, melancholic features, individual atypical
symptoms and other symptoms of depression were not significantly different. The
presence of DSM-IV atypical features predicted bipolar II diagnosis with 63% probability."
[Abstract]

Benazzi
F.Early-onset versus late-onset bipolar II chronic depression.
Depress Anxiety 2001;13(1):45-9 "Age at onset is an important dimension
in the classification of mood disorders. Recent findings on early-onset (EO) versus
late-onset (LO) unipolar chronic depressions support this subtyping. The aim of
the present study was to determine clinical differences between EO and LO bipolar
II chronic depression and to support this subtyping also in bipolar II. Eighty-seven
consecutive bipolar II chronic depression outpatients were interviewed with the
Structured Clinical Interview for DSM-IV, the Montgomery Asberg Depression Rating
Scale, and the Global Assessment of Functioning scale. EO cut-offs were 21 and
23 years of age. Variables, studied with linear and logistic regression, were
age, gender, age at onset, illness duration, recurrences, atypical, melancholic,
and psychotic features, axis I comorbidity, and severity. Lower age at onset was
significantly associated with lower age, longer illness duration, less psychosis,
less severity, more atypical features, and more axis I comorbidity. Results support
the subtyping of bipolar II chronic depression in EO and LO on the basis of different
clinical features." [Abstract]

Benazzi
F.Major depressive episodes with hypomanic symptoms are common
among depressed outpatients. Compr Psychiatry 2001 Mar-Apr;42(2):139-43
"Depressive mixed states (major depressive episodes [MDE] with some hypomanic
symptoms) are not classified in DSM-IV. The aim of the present study was to determine
the prevalence of depressive mixed states in depressed outpatients, and to compare
bipolar II with unipolar depressive mixed states. Seventy consecutive bipolar
II and unipolar depressed outpatients were interviewed using the DSM-IV Structured
Clinical Interview (SCID). At least one hypomanic symptom was present in 90% of
patients, and three or more in 28.5%. Symptoms of depressive mixed states included
irritable mood, distractibility, racing thoughts, and increased talking. Bipolar
II subjects had more concurrent hypomanic symptoms (three or more in 48.7% v 3.2%,
P = 0.000). Depressive mixed states with three or more hypomanic symptoms correctly
classified 70.0% of bipolar II subjects. These findings have important treatment
implications, as antidepressants may worsen the symptoms of depressive mixed states,
and mood stabilizers can be useful." [Abstract]

Sato,
Tetsuya, Bottlender, Ronald, Kleindienst, Nikolaus, Moller, Hans-JurgenSyndromes and Phenomenological Subtypes Underlying Acute Mania: A Factor Analytic
Study of 576 Manic Patients Am J Psychiatry 2002 159: 968-974
"OBJECTIVE: There are no factor analytic studies specifically including symptoms
representative of depressive inhibition among manic patients, although Kraepelin
described several mixed affective states with depressive inhibition. There is
controversy as to whether atypical manic features such as aggression, psychosis,
and depression are likely to coexist among manic patients. The authors goal
was to examine this controversy. METHOD: They used a standardized instrument to
assess the presence or absence of 37 psychiatric symptoms in 576 consecutive inpatients
who were diagnosed as having DSM-IV manic episode, nonmixed or mixed. RESULTS:
A principal-component analysis followed by varimax rotation extracted seven independent
interpretable factors (depressive mood, irritable aggression, insomnia, depressive
inhibition, pure manic symptoms, emotional lability/agitation, and psychosis)
that were relatively stable across several patient groups. A subsequent cluster
analysis identified four phenomenological subtypes underlying acute mania: pure,
aggressive, psychotic, and depressive (mixed) mania. Several variables, including
gender, suicidality, and outcome of treatments, significantly differentiated the
subtypes. CONCLUSIONS: In patients with mania, depressive inhibition may be a
salient syndrome independent of depressive mood, lending some support to Kraepelins
classification of mixed manic states on the basis of the permutations of three
elementsthought disorder, mood, and psychomotor activity. Depressive inhibition,
together with depressive mood and emotional lability/agitation, appears to be
an important phenomenological element of mixed states. Atypical manic features
such as aggression, psychosis, and depression are not likely to coexist, but they
are likely separately to characterize several different subtypes potentially underlying
acute mania." [Abstract]

Dilsaver
SC, Chen YR, Shoaib AM, Swann AC.Phenomenology of mania: evidence
for distinct depressed, dysphoric, and euphoric presentations.
Am J Psychiatry 1999 Mar;156(3):426-30 "OBJECTIVE: A substantial number
of manic episodes include conspicuous depressive symptoms. Manic episodes have
been clinically classified a posteriori using preset criteria. The aim of this
study was to investigate the possibility that there might be a natural division
of manic episodes into clinical types. METHOD: One hundred and five inpatients
met Research Diagnostic Criteria and DSM-III-R criteria for manic episodes and
were rated before institution of pharmacological treatment. The authors conducted
a factor analysis of 37 behavior rating items from the Schedule for Affective
Disorders and Schizophrenia. The resulting factors were used as independent variables
in a cluster analysis of the patients. RESULTS: This analysis revealed four factors
corresponding to manic activation, depressed state, sleep disturbance, and irritability/paranoia.
Cluster analysis separated the patients into two groups. One included patients
with major depressive disorder and mania. Blind, a priori clinical classification
into classic and mixed mania (mania plus depression) showed that all of the patients
in the depressed cluster, and about 40% of those in the nondepressed cluster,
were in a mixed state according to clinical criteria. Comparison of the clinically
mixed and nonmixed patients in the nondepressed cluster revealed that the mixed
patients in that cluster had higher scores for items related to anger, worry,
dysphoria, and irritability. CONCLUSIONS: These data suggest that manic episodes
can be naturalistically classified as classic (predominately euphoric), dysphoric,
or depressed." [Abstract]

Benazzi
F.Atypical depression with hypomanic symptoms.
J Affect Disord 2001 Jul;65(2):179-83 "BACKGROUND: Depressive mixed states
(major depressive episodes with some hypomanic symptoms) (DMS) are not classified
in DSM-IV and are understudied. The aims of this study were to find the prevalence
and clinical features of DMS in atypical depression. METHODS: A total of 87 bipolar
II and unipolar depressed outpatients were interviewed within the DSM-IV Structured
Clinical Interview. RESULTS: More than two hypomanic symptoms were present in
50.0% of the atypical and 20.3% of the non-atypical depression cases (P=0.006).
DMS mainly included irritable mood, distractibility, racing thoughts, and increased
talking. LIMITATIONS: There was a single interviewer, and it was a non-blind,
cross-sectional assessment, with bipolar II reliability. CONCLUSIONS: Findings
have treatment implications, as antidepressants may worsen DMS, and mood stabilizers
may improve it." [Abstract]

Benazzi
F.Prevalence of bipolar II disorder in atypical depression.
Eur Arch Psychiatry Clin Neurosci 1999;249(2):62-5 "The diagnostic validity
of atypical depression is based on its superior response to monoamine oxidase
inhibitors compared to tricyclic antidepressants, and on latent class analysis.
The studies on atypical depression have often not included bipolar patients. The
aim of the present study was to find the prevalence of bipolar II disorder among
DSM-IV atypical depression outpatients. Bipolar II and unipolar atypical depressions
were also compared to find if they were variants of the same disorder or if instead
they were different disorders. One hundred and forty consecutive unipolar and
bipolar II outpatients, presenting for treatment of an atypical major depressive
episode, were interviewed with the Structured Clinical Interview for DSM-IV, the
Montgomery Asberg Depression Rating Scale (MADRS), and the Global Assessment of
Functioning Scale. The prevalence of bipolar II disorder was 64.2%. The age at
baseline and onset were significantly lower in bipolar II versus unipolar patients.
All the other variables (MADRS items, duration of illness, severity, gender, psychosis,
comorbidity, chronicity, recurrences) were not significantly different. The prevalence
of bipolar II disorder among atypical depressed outpatients was higher than previously
reported." [Abstract]

Benazzi
F.The Montgomery Asberg Depression Rating Scale in bipolar II and
unipolar out-patients: a 405-patient case study. Psychiatry
Clin Neurosci 1999 Jun;53(3):429-31 "The aim of the present study was
to find if the Montgomery Asberg Depression Rating Scale (MADRS) can identify
symptom differences between bipolar II and unipolar depression. Four hundred and
five consecutive bipolar II and unipolar depressed out-patients were interviewed
with the Comprehensive Assessment of Symptoms and History structured interview,
following DSM-IV criteria, the MADRS, and the Global Assessment of Functioning
Scale. The Montgomery Asberg Depression Rating Scale items were not significantly
different between bipolar II and unipolar patients. Comparisons among atypical
and non-atypical bipolar II and unipolar patients showed that only MADRS items
of 'reduced sleep' and 'reduced appetite' were significantly different between
atypical and non-atypical patients." [Abstract]

Woods
SW, Money R, Baker CB.Does the manic/mixed episode distinction
in bipolar disorder patients run true over time? Am J Psychiatry
2001 Aug;158(8):1324-6 "OBJECTIVE: The authors sought to determine whether
the manic/mixed episode distinction in patients with bipolar disorder runs true
over time. METHOD: Over an 11-year period, the observed distribution of manic
and mixed episodes (N=1,224) for patients with three or more entries in the management
information system of a community mental health center (N=241) was compared to
the expected distribution determined by averaging 1,000 randomly generated simulations.
RESULTS: Episodes were consistent (all manic or all mixed) in significantly more
patients than would be expected by chance. CONCLUSIONS: These data suggest a pattern
of diagnostic stability over time for manic and mixed episodes in patients with
bipolar disorder. Careful prospective studies of this issue are needed."
[Abstract]

Benazzi
F.Is 4 days the minimum duration of hypomania in bipolar II disorder?
Eur Arch Psychiatry Clin Neurosci 2001;251(1):32-4 "DSM-IV requires that
bipolar II disorder has hypomania with a minimum duration of 4 days, a cutoff
not based on data. The study aim was to test if hypomania lasting 2 to 3 days
could identify a group of bipolar II with typical clinical features of bipolar
disorders. Consecutively, 65 unipolar and 103 bipolar II major depressive episode
(MDE) outpatients were interviewed with the Structured Clinical Interview for
DSM-IV. Almost all had had 2 to 3 days of hypomania, and all had had more than
one hypomania. Typical clinical variables distinguishing bipolar from unipolar
disorders (age at onset, atypical features, and recurrences) were compared. Bipolar
II had significantly lower age at onset, more recurrences, and more atypical features.
Findings suggest that hypomania lasting 2 to 3 days may identify a bipolar II
group having typical features of bipolar disorders." [Abstract]

Benazzi
F, Rihmer Z.Sensitivity and specificity of DSM-IV atypical features
for bipolar II disorder diagnosis. Psychiatry Res 2000
Apr 10;93(3):257-62 "The aim of the study was to find the sensitivity
and the specificity of DSM-IV atypical features (mood reactivity, weight gain,
appetite increase, hypersomnia, leaden paralysis, interpersonal rejection sensitivity)
for the diagnosis of bipolar II disorder. Consecutive 557 unipolar (54.9%) and
bipolar II (45.0%) major depressive episode (MDE) outpatients were interviewed
with the Structured Clinical Interview for DSM-IV and the Global Assessment of
Functioning Scale. Bipolar II was diagnosed broadly, with a minimum duration of
hypomania of at least some days, instead of the 4 days required by DSM-IV. MDE
with atypical features was significantly more common in bipolar II patients. For
the diagnosis of bipolar II disorder, MDE with atypical features, sensitivity
was 0.45, and specificity was 0. 74. Among individual atypical features, hypersomnia
had the best combination of sensitivity (0.35) and specificity (0.81). Combinations
of two and three features did not improve sensitivity and specificity. As the
diagnosis of past hypomania may not be very reliable from a patient's interview,
atypical features may be an important marker of bipolar II disorder." [Abstract]

Benazzi
F.Atypical bipolar II depression compared with atypical unipolar
depression and nonatypical bipolar II depression. Psychopathology
2000 Mar-Apr;33(2):100-2 "Aim of the study was to find out whether atypical
bipolar II depression was distinct from both atypical unipolar depression and
nonatypical bipolar II depression. Seventy-nine consecutive atypical bipolar II
depressed outpatients were compared with 42 consecutive atypical unipolar depressed
outpatients and with 53 consecutive nonatypical bipolar II depressed outpatients.
Among the variables studied (age at intake, age at onset, female gender, duration
of illness, psychosis, comorbidity, chronicity, recurrences, severity), age at
intake and onset were significantly lower in the atypical bipolar II group than
in the other groups. The other variables, apart from psychosis, were not significantly
different. Findings suggest that atypical bipolar II depression may have an age
at onset different from that of atypical unipolar depression and nonatypical bipolar
II depression. As different ages at onset may identify distinct subtypes of depression,
this finding might suggest that atypical bipolar II depression may be distinct
from both atypical unipolar depression and nonatypical bipolar II depression.
Copyright 2000 S. Karger AG, Basel." [Abstract]

Benazzi
F.Prevalence and clinical features of atypical depression in depressed
outpatients: a 467-case study. Psychiatry Res 1999 Jun
30;86(3):259-65 "The prevalence of DSM-IV atypical depression and differences
between atypical versus non-atypical depression were investigated in 467 unipolar
and bipolar depressed outpatients in private practice. Consecutive outpatients
presenting for treatment of a major depressive episode were assessed with the
Comprehensive Assessment of Symptoms and History following DSM-IV criteria, the
Montgomery-Asberg Depression Rating Scale, and the Global Assessment of Functioning
Scale. The prevalence of atypical depression was 38.1%. Of the variables investigated
(unipolar and bipolar diagnoses, age at onset, gender, psychosis, comorbidity,
chronicity, duration of illness, recurrences, and severity), age at onset was
significantly lower, and female gender, comorbidity, and bipolar II disorder were
significantly more common in atypical than nonatypical depression. Comparisons
between bipolar II atypical depression and unipolar atypical depression did not
show significant differences, apart from age at onset. Findings suggest that there
are important clinical differences between atypical and non-atypical depression
in private practice outpatients." [Abstract]

Benazzi
F.Gender differences in bipolar II and unipolar depressed outpatients:
a 557-case study. Ann Clin Psychiatry 1999 Jun;11(2):55-9
"The aim of the present report was to study gender differences in bipolar
II and in unipolar depressed outpatients. Consecutive 557 bipolar II and unipolar
outpatients presenting for treatment of depression were interviewed with the Structured
Clinical Interview for DSM-IV, the Montgomery Asberg Depression Rating Scale,
and the Global Assessment of Functioning Scale. Atypical features were significantly
more common in bipolar II and in unipolar females than in males, in bipolar II
females than in unipolar females, and in bipolar II males than in unipolar males.
Female gender was significantly associated with atypical features, but not with
diagnosis. Age at intake/onset, duration of illness, severity, recurrences, psychosis,
and chronicity were not significantly different in bipolar II and in unipolar
females and males (apart from comorbidity). Age at onset was significantly lower
in bipolar II females than in unipolar females. This difference was not related
to the higher prevalence of atypical features in bipolar II females." [Abstract]

Perugi
G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A, Vignoli S,
Bemi E.The high prevalence of "soft" bipolar (II) features
in atypical depression. Compr Psychiatry 1998 Mar-Apr;39(2):63-71
"Seventy-two percent of 86 major depressive patients with atypical features
as defined by the DSM-IV and evaluated systematically were found to meet our criteria
for bipolar II and related "soft" bipolar disorders; nearly 60% had
antecedent cyclothymic or hyperthymic temperaments. The family history for bipolar
disorder validated these clinical findings. Even if we limit the diagnosis of
bipolar II to the official DSM-IV threshold of 4 days of hypomania, 32.6% of atypical
depressives in our sample would meet this conservative threshold, a rate that
is three times higher than the estimates of bipolarity among atypical depressives
in the literature. By definition, mood reactivity was present in all patients,
while interpersonal sensitivity occurred in 94%. Lifetime comorbidity rates were
as follows: social phobia 30%, body dysmorphic disorder 42%, obsessive-compulsive
disorder 20%, and panic disorder (agoraphobia) 64%. Both cluster A (anxious personality)
and cluster B (e.g., borderline and histrionic) personality disorders were highly
prevalent. These data suggest that the "atypicality" of depression is
favored by affective temperamental dysregulation and anxiety comorbidity, clinically
manifesting in a mood disorder subtype that is preponderantly in the realm of
bipolar II. In the present sample, only 28% were strictly unipolar and characterized
by avoidant and social phobic features, without histrionic traits." [Abstract]

Benazzi
F.Is atypical depression a moderate severity depression? A 536-case
study. J Psychiatry Neurosci 1999 May;24(3):244-7 "OBJECTIVE:
To determine if atypical depression is less common among outpatients with severe
depression than among those with nonsevere depression. DESIGN: Case series. SETTING:
Private practice. PATIENTS: Five hundred and thirty-six consecutive outpatients
presenting for treatment of unipolar or bipolar II depression. OUTCOME MEASURES:
Prevalence of atypical depression among patients with severe depression (Global
Assessment of Functioning Scale [GAF] score of 50 or less) and nonsevere depression.
RESULTS: There was no significant difference in the prevalence of atypical depression
between patients with severe and nonsevere depression. CONCLUSIONS: Results do
not support previous studies that atypical depression is usually of moderate severity.
A rating scale like the GAF, which assesses both symptom severity and impairment
of functioning, may give a more complete assessment of depression severity than
a symptoms rating scale (used in previous studies), which does not cover atypical
features and does not assess functioning." [Abstract]

Benazzi
F.Late-life atypical major depressive episode: a 358-case study
in outpatients. Am J Geriatr Psychiatry 2000 Spring;8(2):117-22
"The author compared the prevalence and symptoms of DSM-IV major depressive
episode (MDE) with atypical features between older and younger MDE outpatients
(N = 358). Atypical MDE was present in 55.0% of MDE patients under age 60 and
in 28.1% age 60 and over (P = 0.0000). Bipolar II disorder was present in 56.4%
of younger patients, and in 23.9% of late-life patients (P = 0.0000). Late-life
atypical MDE patients had less interpersonal-rejection sensitivity. Prevalence
of atypical MDE seems lower among late-life MDE outpatients than among younger
MDE outpatients, which may be related to the decrease with aging in the prevalence
of patients with bipolar II MDE, where there is a higher prevalence of atypical
features." [Abstract]

Benazzi
F.Bipolar II depression with melancholic features.
Ann Clin Psychiatry 2000 Mar;12(1):29-33 "Bipolar II depression with
melancholic features has been understudied. The aims of the present study were
to find the prevalence of melancholic features in bipolar II depression and in
unipolar depression, and to compare melancholic with nonmelancholic bipolar II/
unipolar depression in private practice. One hundred and sixty two consecutive
unipolar and bipolar II depressed outpatients were interviewed with the DSM-IV
Structured Clinical Interview, the Montgomery-Asberg Depression Rating Scale,
and the Global Assessment of Functioning Scale. Melancholic features were present
in 19.2% of bipolar II patients and in 22.6% of unipolar patients, a nonsignificant
difference. Melancholic bipolar II patients versus nonmelancholic bipolar II patients
had significantly more psychosis and higher severity. All the other variables
(age, age at onset, gender, illness duration, recurrences, atypical features,
chronicity, comorbidity) were not significantly different. Melancholic bipolar
II patients versus melancholic unipolar patients were not significantly different.
Nonmelancholic bipolar II patients versus nonmelancholic unipolar patients had
significantly lower age, lower age at onset, more atypical features, and more
comorbidity. The prevalence of melancholic features in bipolar II depression in
private practice was higher than previously reported in academic centers."
[Abstract]

Parker
G, Roy K, Wilhelm K, Mitchell P, Hadzi-Pavlovic D.The nature of
bipolar depression: implications for the definition of melancholia.
J Affect Disord 2000 Sep;59(3):217-24 "AIM: To examine if melancholic
depression is over-represented in those with 'bipolar depression' and, if confirmed,
to use that phenomenon to assist the clinical definition of melancholia. METHODS:
We contrast 83 bipolar and 904 unipolar depressed patients on three melancholic
sub-typing systems (DSM, Clinical and CORE system) and compare representation
of their clinical depressive features. RESULTS: By all three melancholic sub-typing
systems, the bipolar patients were more likely to receive diagnoses of 'melancholia'
and of psychotic depression. To the extent that this differential prevalence of
depressive sub-types was reflected in varying patterns of clinical features, we
so indirectly identified a set of items defining 'melancholia'. By such a strategy,
melancholia was most clearly distinguished by behaviourally-rated psychomotor
disturbance. While a number of 'endogeneity symptoms' were significantly over-represented,
logistic regression analyses refined the set to psychomotor disturbance (both
as a symptom and as a sign) and pathological guilt. We also established a distinctly
higher prevalence of bipolar depression in those where a refined diagnosis of
melancholia was made. CONCLUSIONS: Bipolar depression appears to be more likely
to be 'melancholic' in type, thus providing an indirect strategy for the clinical
definition of melancholia." [Abstract]

Braunig
P, Kruger S, Shugar G.Prevalence and clinical significance of catatonic
symptoms in mania. Compr Psychiatry 1998 Jan-Feb;39(1):35-46
"The study investigates the prevalence, clinical characteristics, and implications
of catatonic symptoms in mania. Sixty-one inpatients with DSM-III-R bipolar disorder
(BD), manic or mixed episode, established by the Structured Clinical Interview
for DSM-III-R (SCID) were assessed for the presence of catatonic by a 21-item
rating scale. Nineteen patients fulfilled criteria for catatonic mania, exhibiting
between five and 16 catatonic symptoms. Catatonic manics had more mixed episodes,
more severe manic symptoms, more general psychopathology, a higher prevalence
of comorbidity, a longer hospitalization, and lower Global Assessment of Functioning
(GAF) scores than the noncatatonics. The results indicate that catatonic symptoms
are a marker of a more severe course and outcome in mania." [Abstract]

Kruger
S, Cooke RG, Spegg CC, Braunig P.Relevance of the catatonic syndrome
to the mixed manic episode. J Affect Disord. 2003 May;74(3):279-85."BACKGROUND:
Catatonic symptoms have been associated with mixed mania in the older psychiatric
literature, however, to date no systematic studies have been performed to assess
their frequency in these patients. METHOD: Ninety-nine patients with bipolar disorder
manic or mixed episode were assessed for the presence of catatonia. RESULTS: Thirty-nine
patients fulfilled criteria for mixed mania of whom 24 were catatonic. Among the
patients with pure mania, only three were catatonic. Eighteen catatonic patients
with mixed mania required admission to the acute care unit (ACU). LIMITATIONS:
Our findings only apply to severely ill patients with mixed mania who require
ACU admission. Nevertheless, it is important to know, that the likelihood of overlooking
catatonia in less severely ill patients with mixed mania is low and that it does
not need to be routinely assessed on a general ward. CONCLUSIONS: Catatonia is
frequent in mania and linked to the mixed episode. Catatonia in mixed mania is
likely to be found among the severely ill group of patients with mixed mania,
who require emergency treatment." [Abstract]

Chang
KD, Keck PE Jr, Stanton SP, McElroy SL, Strakowski SM, Geracioti TD Jr.Differences in thyroid function between bipolar manic and mixed states.
Biol Psychiatry 1998 May 15;43(10):730-3 "BACKGROUND: High rates of thyroid
axis abnormalities have been reported in most studies of patients with rapid-cycling
bipolar disorder. Mixed states share similarities with rapid-cycling, including
close temporal occurrence of manic and depressive symptoms, predominance in women,
poor outcome, and less robust response to lithium compared with pure mania; however,
thyroid axis abnormalities have not been well studied in mixed mania. METHODS:
To test the hypothesis that mixed states are associated with a higher prevalence
of hypothyroidism than pure mania, immunoreactive triiodothyronine (T3), thyroxine
(T4), and thyroid-stimulating hormone (TSH) concentrations were determined from
serum obtained at the time of admission in 37 consecutive patients with DSM-III-R
bipolar disorder, manic or mixed. RESULTS: The mean TSH concentration was significantly
higher, and the mean T4 concentration was significantly lower in patients with
mixed mania compared with pure mania. There were no significant differences in
T3 concentration or in previous lithium exposure. CONCLUSIONS: These findings
suggest thyroid axis dysfunction is more common in bipolar mixed than in bipolar
manic patients." [Abstract]

Arnold
LM, McElroy SL, Keck PE Jr.The role of gender in mixed mania.
Compr Psychiatry 2000 Mar-Apr;41(2):83-7 "This article reviews the literature
regarding possible gender differences in adults with mixed mania. Studies examining
gender differences in the prevalence of mixed mania, biological abnormalities,
suicidality, long-term outcome, and treatment response were analyzed. Data from
these studies suggest that mixed mania may occur more commonly in women than in
men, especially when defined by narrow criteria. There were no significant differences
between men and women with mixed mania in biological abnormalities, suicidality,
outcome, and treatment response." [Abstract]

Benazzi
F.Exploring aspects of DSM-IV interpersonal sensitivity in bipolar
II. J Affect Disord 2000 Oct;60(1):43-6 "BACKGROUND:
The aim of the study was to find the prevalence of interpersonal rejection sensitivity
(IRS) (a personality trait in DSM-IV) in bipolar II and unipolar depression. METHODS:
557 consecutive unipolar and bipolar II outpatients, presenting for depression
treatment, were interviewed with the DSM-IV Structured Clinical Interview and
the Global Assessment of Functioning Scale. DSM-IV atypical features criteria
(which include IRS) were followed. RESULTS: IRS was significantly more common
in bipolar II than in unipolar patients (37.8% vs. 20.5%, odds ratio 2.3, P=0.0000).
Sensitivity and specificity for bipolar II diagnosis were 37.8% and 79.4%. CONCLUSIONS:
IRS personality trait seems to be more common in bipolar II than in unipolar depression.
LIMITATIONS: reliability of bipolar II diagnosis, non-blind, cross-sectional assessment,
single interviewer." [Abstract]

Swann
AC, Secunda SK, Koslow SH, Katz MM, Bowden CL, Maas JW, Davis JM, Robins E.Mania: sympathoadrenal function and clinical state.
Psychiatry Res 1991 May;37(2):195-205 "We investigated sympathoadrenal
and sympathetic nervous system activity, catecholamine disposition, and clinical
state in 19 hospitalized manic patients. Severity of the core manic syndrome,
anxiety, and hostility correlated with 24-hour urinary excretion of epinephrine
relative to its metabolites, but only weakly with norepinephrine. Agitation, however,
correlated most strongly and significantly with norepinephrine. Eight of the patients
had mixed states: concurrent manic and depressive syndromes. There were no differences
between mixed and pure manic patients with respect to catecholamine or metabolite
excretion or precursor/product ratios, but mixed manic patients tended to have
higher excretion of norepinephrine and had increased variance with respect to
catecholamine measures. These data suggest that the function of the adrenal medulla,
whether directly or indirectly, is important in the symptoms of both mixed and
pure mania." [Abstract]

Dell'Osso
L, Pini S, Cassano GB, Mastrocinque C, Seckinger RA, Saettoni M, Papasogli A,
Yale SA, Amador XF.Insight into illness in patients with mania,
mixed mania, bipolar depression and major depression with psychotic features.Bipolar
Disord. 2002 Oct;4(5):315-22."BACKGROUND: Poor insight into illness is
a common feature of bipolar disorder and one that is associated with poor clinical
outcome. Empirical studies of illness awareness in this population are relatively
scarce with the majority of studies being published over the previous decade.
The study reported here sought to replicate previous report findings that bipolar
patients frequently show high levels of poor insight into having an illness. We
also wanted to examine whether group differences in insight exist among bipolar
manic, mixed and unipolar depressed patients with psychotic features. METHODS:
A cohort of 147 inpatients with DSM-III-R bipolar disorder and 30 with unipolar
depression with psychotic features, were evaluated in the week prior to discharge
using the Structured Clinical Interview for DSM-III-R-Patient Edition (SCID-P),
the Brief Psychiatric Rating Scale (BPRS) and the Scale to assess Unawareness
of Mental Disorder (SUMD). RESULTS: Insight into specific aspects of the illness
was related to the polarity of mood episode: patients with mania showed significantly
poorer insight compared with those with mixed mania, bipolar depression and unipolar
depression. A linear regression analysis using SUMD score as the dependent variable
and symptoms of mania as the independent variable found that specific manic symptoms
did not account for level of insight. Similar results were obtained when the mean
insight scores of patients with and without grandiosity were contrasted. CONCLUSIONS:
We hypothesize that the lack of association between level of insight and total
number of manic symptoms or with specific manic symptoms may be related to the
persistence of subsyndromal symptoms in patients remitting from a manic episode."
[Abstract]